PTP4A1

Summary

PTP4A1 (protein tyrosine phosphatase 4A1, HGNC:9634) is a protein-coding gene on chromosome 6q12, encoding Protein tyrosine phosphatase type IVA 1 (Q93096). Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. It is a selective cancer dependency (DepMap: 11.3% of cell lines).

This gene encodes a member of a small class of prenylated protein tyrosine phosphatases (PTPs), which contain a PTP domain and a characteristic C-terminal prenylation motif. The encoded protein is a cell signaling molecule that plays regulatory roles in a variety of cellular processes, including cell proliferation and migration. The protein may also be involved in cancer development and metastasis. This tyrosine phosphatase is a nuclear protein, but may associate with plasma membrane by means of its prenylation motif. Pseudogenes related to this gene are located on chromosomes 1, 2, 5, 7, 11 and X.

Source: NCBI Gene 7803 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 1 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 11.3% of screened cell lines
• MANE Select transcript: NM_003463

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9634
Approved symbol	PTP4A1
Name	protein tyrosine phosphatase 4A1
Location	6q12
Locus type	gene with protein product
Status	Approved
Aliases	PTPCAAX1, PRL-1, PRL1
Ensembl gene	ENSG00000112245
Ensembl biotype	protein_coding
OMIM	601585
Entrez	7803

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000470661, ENST00000473334, ENST00000626021, ENST00000639568, ENST00000648894, ENST00000672924, ENST00000673199

RefSeq mRNA: 14 — MANE Select: NM_003463 NM_001385254, NM_001385255, NM_001385256, NM_001385257, NM_001385258, NM_001385259, NM_001385260, NM_001385262, NM_001385263, NM_001385265, NM_001385266, NM_001385267, NM_001385268, NM_003463

CCDS: CCDS4965

Canonical transcript exons

ENST00000626021 — 6 exons

Exon	Start	End
ENSE00000757682	63578437	63578529
ENSE00000757684	63578898	63579028
ENSE00000757686	63579257	63579331
ENSE00000999818	63576436	63576985
ENSE00003768455	63580057	63583588
ENSE00003918264	63572480	63572719

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 90.6000 / max 2081.8262, expressed in 1825 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68376	38.9867	1813
68378	37.1329	1817
68377	12.1030	1799
68355	0.6295	27
68391	0.5254	288
68384	0.5133	275
68373	0.1866	39
68372	0.0941	32
68365	0.0849	17
68354	0.0840	10

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	98.93	gold quality
islet of Langerhans	UBERON:0000006	98.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.49	gold quality
cortical plate	UBERON:0005343	98.46	gold quality
liver	UBERON:0002107	98.39	gold quality
right lobe of liver	UBERON:0001114	98.37	gold quality
rectum	UBERON:0001052	98.29	gold quality
gastrocnemius	UBERON:0001388	97.98	gold quality
ganglionic eminence	UBERON:0004023	97.91	gold quality
skeletal muscle tissue	UBERON:0001134	97.86	gold quality
muscle of leg	UBERON:0001383	97.81	gold quality
ventricular zone	UBERON:0003053	97.43	gold quality
smooth muscle tissue	UBERON:0001135	96.92	gold quality
muscle tissue	UBERON:0002385	96.76	gold quality
gall bladder	UBERON:0002110	96.51	gold quality
mucosa of transverse colon	UBERON:0004991	96.38	gold quality
bone marrow	UBERON:0002371	96.21	gold quality
duodenum	UBERON:0002114	95.91	gold quality
stromal cell of endometrium	CL:0002255	95.68	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.62	gold quality
pancreas	UBERON:0001264	95.56	gold quality
endometrium	UBERON:0001295	95.54	gold quality
placenta	UBERON:0001987	95.54	gold quality
right testis	UBERON:0004534	95.03	gold quality
left testis	UBERON:0004533	94.99	gold quality
corpus callosum	UBERON:0002336	94.79	gold quality
bone marrow cell	CL:0002092	94.62	gold quality
vermiform appendix	UBERON:0001154	94.39	gold quality
right adrenal gland cortex	UBERON:0035827	94.38	gold quality
tonsil	UBERON:0002372	94.12	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.56
E-MTAB-10553	yes	21.42
E-GEOD-125970	yes	14.98
E-ANND-3	yes	2.90
E-MTAB-6379	no	2156.14
E-GEOD-93593	no	7.86

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, TP53

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 32)

• PRL-1 function is regulated in a cell cycle-dependent manner and implicate PRL-1 in regulating progression through mitosis, possibly by modulating spindle dynamics (PMID:12235145)
• PRL phosphatases increase cell proliferation by stimulating progression from G1 into S phase (PMID:14643450)
• PRL-1 phosphatase has a trimeric structure which reveals an active enzyme conformation and regulation mechanisms (PMID:15571731)
• PRL-1 mRNA expression was not significantly higher in malignant compared to benign breast tissue. (PMID:16832410)
• PRL-1 expression levels varied considerably both between tissue types and cell type examined. Widespread expression of PRL-1 in multiple organ systems suggests an important functional role for these enzymes in normal tissue homeostasis. (PMID:16957164)
• Colonic adenocarcinoma cells have the ability to produce PTP4A1, PTP4a2, and PTP4A3, which may relate to the lymph node metastasis of colonic adenocarcinoma. (PMID:17440740)
• that trimerization may be a general property for all PRL enzymes, and that PRL1 trimer formation is essential for the PRL1-mediated cell growth and migration. (PMID:17656357)
• PRL-1 and PRL-3 mRNAs may be involved in and used to predict the metastasis of esophageal squamous cell carcinoma. Possibility of using PRL-1 and PRL-3 as therapeutical target. (PMID:18684031)
• the new oncogenic p53 target, PRL-1, may contribute to tumor development by the downregulation of p53 by a negative feedback mechanism. (PMID:18997816)
• Increased PRL1 expression results in activation of Src and ERK1/2, which stimulates MMP2 and MMP9 production, leading to increased cell migration and invasion. (PMID:19199380)
• phosphatase of regenerating liver activity is controlled by the redox environment and its C-terminal residues (PMID:19341304)
• PRL-1 binding to p115 RhoGAP provides a coordinated mechanism underlying ERK1/2 and RhoA activation (PMID:22009749)
• Data conclude that the PHF3-PTP4A1 region appears to harbor a causal locus for alcohol dependence, and proteins encoded by PHF3 and/or PTP4A1 might play a functional role in the disorder. (PMID:22096494)
• Studies indicate that PRL-1 and PRL-2 and PRL-3 are oncogenes and belong to the few phosphatases that lead to the development of cancer. (PMID:22413991)
• upregulation of PRL-1 protein correlates with shortened patient survival in human hepatocellular carcinoma (PMID:22484636)
• PTP4A1-PHF3-EYS variants were associated with alcohol dependence. (PMID:23324950)
• Results suggest that TRP32 maintains the reduced state of PRL and thus regulates the biological function of PRL. (PMID:23362275)
• Upregulation of PRL-1 expression is inversely correlated with miR-26a in primary cervical cancer tissues. (PMID:24939702)
• We confirmed with our previous findings that PTP4A1-PHF3-EYS variants were significantly associated with alcohol dependence. (PMID:24961364)
• Data indicate that protein-tyrosine-phosphatase of regenerating liver 1 (PRL1) gene was expressed much more highly in prostate cancer (PCa) than in nonneoplastic prostate samples. (PMID:24968948)
• Data highlight the oncogenic function of PRL-1 in HCC invasion and metastasis. (PMID:25003523)
• miR-601 inhibits growth and invasion of breast cancer cells by targeting PTP4A1. (PMID:27044835)
• Results showed that SIAH1 and PTP4A1 expression was regulated by mir-944 in breast cancer cells. miR-944 binds directly the 3 UTR of their promotor region. (PMID:27377268)
• PTP4A1 was overexpressed in ICC and played an important role in the progression and metastasis of ICC. The functional role of PTP4A1 was assumed to be acted by activation PI3K/AKT signaling and promoting the EMT process through two pivotal transcriptional factors Zeb1 and Snail. (PMID:27655691)
• PTP4A1 is highly expressed in fibroblasts from patients with systemic sclerosis and enhances pro-fibrotic TGFbeta signaling in these cells. (PMID:29057934)
• PTP4A1 is a direct downstream target of miR-1271 in the hepatocellular carcinoma. (PMID:29345291)
• PRL mRNA transcription was stimulated by Mg(2+) depletion. A series of analyses revealed the activation and the crucial importance of signal transducer and activator of transcription 1 in this process. Collectively, these results implicate PRL in maintaining cellular Mg(2+) homeostasis. (PMID:29487165)
• Overexpression of miR-339-5p enhanced radiosensitivity of A549 and H460 cells by inhibiting cell viability, increasing apoptosis, inducing cell cycle arrest, and suppressing cell proliferation. Further exploration validated that miR-339-5p can target phosphatases of regenerating liver-1 (PRL-1) in lung cancer cells. (PMID:30462625)
• These results provide evidence indicating a regulatory role of PRL-1 during Immunological Synapse assembly and highlight the involvement of PRLs in immune responses by mature T cells. (PMID:30515156)
• LncRNA NEAT1 promotes cell proliferation, migration, and invasion via the miR-186-5p/PTP4A1 axis in cholangiocarcinoma. (PMID:33502823)
• GINS2 regulates the proliferation and apoptosis of colon cancer cells through PTP4A1. (PMID:35137928)
• Endothelial PTP4A1 mitigates vascular inflammation via USF1/A20 axis-mediated NF-kappaB inactivation. (PMID:36534975)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptp4a1	ENSDARG00000006242
mus_musculus	Ptp4a1	ENSMUSG00000026064
mus_musculus	Ptp4a1	ENSMUSG00000117310
rattus_norvegicus	Ptp4a1	ENSRNOG00000011771
rattus_norvegicus	AABR07041247.1	ENSRNOG00000030645
rattus_norvegicus		ENSRNOG00000086578

Paralogs (8): CDC14A (ENSG00000079335), CDC14B (ENSG00000081377), CDKN3 (ENSG00000100526), PALD1 (ENSG00000107719), PTPDC1 (ENSG00000158079), PTP4A2 (ENSG00000184007), PTP4A3 (ENSG00000184489), CDC14C (ENSG00000218305)

Protein

Protein identifiers

Protein tyrosine phosphatase type IVA 1 — Q93096 (reviewed: Q93096)

Alternative names: PTP(CAAXI), Protein-tyrosine phosphatase 4a1, Protein-tyrosine phosphatase of regenerating liver 1

All UniProt accessions (2): A0A3B3ISR8, Q93096

UniProt curated annotations — full annotation on UniProt →

Function. Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. May play a role in the development and maintenance of differentiating epithelial tissues. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis.

Subunit / interactions. Homotrimer. Interacts with ATF5. Interacts with tubulin.

Subcellular location. Cell membrane. Early endosome. Endoplasmic reticulum. Cytoplasm. Cytoskeleton. Spindle. Nucleus.

Tissue specificity. Expressed in bone marrow, lymph nodes, T lymphocytes, spleen, thymus and tonsil. Overexpressed in tumor cell lines.

Post-translational modifications. Farnesylated. Farnesylation is required for membrane targeting. Unfarnesylated forms are shifted into the nucleus.

Activity regulation. Inhibited by sodium orthovanadate and pentamidine.

Induction. Strongly down-regulated upon tetrodotoxin treatment.

Similarity. Belongs to the protein-tyrosine phosphatase family.

RefSeq proteins (14): NP_001372183, NP_001372184, NP_001372185, NP_001372186, NP_001372187, NP_001372188, NP_001372189, NP_001372191, NP_001372192, NP_001372194, NP_001372195, NP_001372196, NP_001372197, NP_003454* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR050561	PTP	Family

Pfam: PF22785

Enzyme classification (BRENDA):

• EC 3.1.3.16 — protein-serine/threonine phosphatase (BRENDA: 92 organisms, 641 substrates, 468 inhibitors, 127 Km, 67 kcat entries)

Substrate kinetics (BRENDA)

59 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.023–0.862	22
4-NITROPHENYL PHOSPHATE	0.0028–12.7	13
P-NITROPHENYL PHOSPHATE	3–200	11
RRAPTVA	0.058–1.954	4
PHOSPHOCASEIN	0.0001–0.002	3
PHOSPHOHISTONE	0.0023–0.0723	3
PHOSPHORYLATED MYOSIN LIGHT CHAIN PEPTIDE	0.01–0.11	3
PHOSPHOSERINE-MYELIN BASIC PROTEIN	0.0004–0.022	3
DLDVPIPGRFDRRVSVAAE	0.0006–0.0138	2
DLDVPIPGRFDRRVY(P)VAAE	0.0025–0.023	2
PHOSPHORYLASE A	0.004–0.021	2
RRA(PT)VA	0.0536–0.308	2
80S-RIBOSOME	0.0027	1
AAAPTVA	0.206	1
AGPALSPVPPV	0.357	1

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (33 total): mutagenesis site 7, strand 7, helix 7, active site 2, binding site 2, chain 1, propeptide 1, disulfide bond 1, domain 1, turn 1, region of interest 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1RXD	X-RAY DIFFRACTION	1.9
5BX1	X-RAY DIFFRACTION	1.9
9MEX	X-RAY DIFFRACTION	2.6
1XM2	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93096-F1	88.39	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 72 (proton donor); 104 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (2): 105–110; 110

Post-translational modifications (2): 170, 170

Disulfide bonds (1): 49–104

Mutagenesis-validated functional residues (7):

Position	Phenotype
13	reduces trimerization.
71	no effect on catalytic activity.
72	80% loss of catalytic activity; delay in progression through g2/m.
104	abolishes enzymatic activity.
131	reduces trimerization.
170	redistributes to the nucleus in resting cells, but still locates to the mitotic spindle in dividing cells. induces defec
171	no effect on subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 310 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, GRUETZMANN_PANCREATIC_CANCER_DN, chr6q12, TTTGTAG_MIR520D, PID_PRL_SIGNALING_EVENTS_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MODULE_16, CACCAGC_MIR138, BROWNE_HCMV_INFECTION_48HR_DN, CATTTCA_MIR203, UEDA_PERIFERAL_CLOCK, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, SNIJDERS_AMPLIFIED_IN_HEAD_AND_NECK_TUMORS

GO Biological Process (3): positive regulation of cell migration (GO:0030335), protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311)

GO Molecular Function (4): protein tyrosine phosphatase activity (GO:0004725), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), spindle (GO:0005819), cytoplasmic side of plasma membrane (GO:0009898), endosome (GO:0005768), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
endomembrane system	2
intracellular membraneless organelle	2
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
dephosphorylation	1
protein modification process	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
endosome	1
cytoplasm	1
microtubule cytoskeleton	1
plasma membrane	1
cytoplasmic side of membrane	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1004 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTP4A1	ATF7	P17544	892
PTP4A1	PTS	Q03393	833
PTP4A1	IL17RD	Q8NFM7	761
PTP4A1	PHF3	Q92576	757
PTP4A1	GABBR1	Q9UBS5	649
PTP4A1	ATF5	Q9Y2D1	649
PTP4A1	UBE2B	P23567	588
PTP4A1	ATF2	P15336	575
PTP4A1	ARHGAP1	Q07960	553
PTP4A1	ARL15	Q9NXU5	506
PTP4A1	ARHGAP4	P98171	501
PTP4A1	K7ELQ4	K7ELQ4	493
PTP4A1	CDC34	P49427	490
PTP4A1	STARD13	Q9Y3M8	463
PTP4A1	RHOA	P06749	453

IntAct

52 interactions, top by confidence:

A	B	Type	Score
PTP4A1	CNNM1	psi-mi:“MI:0915”(physical association)	0.850
RABGGTB	YKT6	psi-mi:“MI:0914”(association)	0.740
PTP4A1	CNNM4	psi-mi:“MI:0914”(association)	0.740
PTP4A2	CNNM4	psi-mi:“MI:0914”(association)	0.740
PTP4A2	PTP4A3	psi-mi:“MI:0914”(association)	0.640
FNTB	BLTP3B	psi-mi:“MI:0914”(association)	0.530
RABGGTB	PIPSL	psi-mi:“MI:0914”(association)	0.530
PTP4A1	ATE1	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
FNTB	YKT6	psi-mi:“MI:0914”(association)	0.530
LHFPL4	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
IL25	PPM1B	psi-mi:“MI:0914”(association)	0.530
PTP4A1	PSMD3	psi-mi:“MI:0914”(association)	0.420
PTP4A1	PSMD3	psi-mi:“MI:2364”(proximity)	0.420
PTP4A1	nleA/espI	psi-mi:“MI:0915”(physical association)	0.370
nleA/espI	PTP4A1	psi-mi:“MI:0915”(physical association)	0.370
Cep55	UMAD1	psi-mi:“MI:0914”(association)	0.350
Kif21b	TCP1	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
AUP1	APOB	psi-mi:“MI:0914”(association)	0.350
LRRC39	GSN	psi-mi:“MI:0914”(association)	0.350
MBLAC2	STAT3	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
PTP4A1	FDFT1	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350

BioGRID (155): PTP4A1 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS), BLMH (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), CNNM3 (Affinity Capture-MS), CNNM4 (Affinity Capture-MS), FDFT1 (Affinity Capture-MS), NUDT12 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A7H0DN78, A2VDT1, O13632, O13926, O41136, O55737, O61722, O70274, O94526, P07239, P0DOQ5, P0DOQ6, P20495, P25044, P27574, P33825, P41415, P43568, P53208, P80994, Q02158, Q02256, Q08649, Q12385, Q12974, Q54DU9, Q5R7J8, Q5UNT1, Q5UQ96, Q5UQD2, Q5UQH3, Q5UR74, Q5XHB2, Q63739, Q6P9X4, Q78EG7, Q85297, Q86AT8, Q86IL4, Q8IG39

Diamond homologs: A0A0R4IVA4, A1L1R5, A2VDT1, A4D256, A6N3Q4, O60729, O61722, O70274, O75365, P81299, Q00684, Q12974, Q1LWL2, Q59NH8, Q5B323, Q5R7J8, Q63739, Q6GQT0, Q6NZK8, Q6P9X4, Q6PFY9, Q78EG7, Q86BN8, Q93096, Q9D658, Q9JLY7, Q9P7H1, Q9TSM6, Q9UNH5, Q9ZQP1, A2A3K4, A7E379, P35821, Q196Z3, Q4CUJ8, Q6NT99, Q86IL4, Q9BVJ7, Q4QEZ7, Q54DU9

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PTP4A1	up-regulates	CDK2
hsa-miR-29c-5p	“down-regulates quantity by repression”	PTP4A1	“post transcriptional regulation”
WEE1	“down-regulates activity”	PTP4A1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1031 predictions. Top by Δscore:

Variant	Effect	Δscore
6:63576434:A:AG	acceptor_gain	1.0000
6:63576435:G:GG	acceptor_gain	1.0000
6:63578425:C:CA	acceptor_gain	1.0000
6:63578425:C:G	acceptor_gain	1.0000
6:63578432:TCCA:T	acceptor_loss	1.0000
6:63578433:CCAG:C	acceptor_loss	1.0000
6:63578434:CA:C	acceptor_loss	1.0000
6:63578436:G:GA	acceptor_loss	1.0000
6:63578525:TTCTT:T	donor_gain	1.0000
6:63578526:TCTT:T	donor_gain	1.0000
6:63578527:CTT:C	donor_gain	1.0000
6:63578528:TT:T	donor_gain	1.0000
6:63578530:G:GG	donor_gain	1.0000
6:63578531:TAAGT:T	donor_loss	1.0000
6:63578532:AAGTA:A	donor_loss	1.0000
6:63578533:AGT:A	donor_loss	1.0000
6:63578890:T:TA	acceptor_gain	1.0000
6:63578894:TTAGG:T	acceptor_loss	1.0000
6:63578896:A:AG	acceptor_gain	1.0000
6:63578896:AG:A	acceptor_gain	1.0000
6:63578897:G:A	acceptor_loss	1.0000
6:63578897:G:GG	acceptor_gain	1.0000
6:63578897:GG:G	acceptor_gain	1.0000
6:63578897:GGATT:G	acceptor_gain	1.0000
6:63578952:T:G	donor_gain	1.0000
6:63579026:G:GT	donor_gain	1.0000
6:63579255:A:AG	acceptor_gain	1.0000
6:63579256:G:GG	acceptor_gain	1.0000
6:63579256:GA:G	acceptor_gain	1.0000
6:63579327:AGACA:A	donor_gain	1.0000

AlphaMissense

1140 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:63576936:T:C	F19S	1.000
6:63576953:C:T	P25S	1.000
6:63576954:C:A	P25Q	1.000
6:63578472:A:C	R47S	1.000
6:63578472:A:T	R47S	1.000
6:63578476:T:C	C49R	1.000
6:63578477:G:A	C49Y	1.000
6:63578907:T:C	F70L	1.000
6:63578909:T:A	F70L	1.000
6:63578909:T:G	F70L	1.000
6:63578913:G:C	D72H	1.000
6:63578913:G:T	D72Y	1.000
6:63578914:A:C	D72A	1.000
6:63578914:A:G	D72G	1.000
6:63578914:A:T	D72V	1.000
6:63578915:T:A	D72E	1.000
6:63578915:T:G	D72E	1.000
6:63578916:G:C	G73R	1.000
6:63578917:G:A	G73D	1.000
6:63578917:G:T	G73V	1.000
6:63578926:C:A	P76Q	1.000
6:63578949:T:A	W84R	1.000
6:63578949:T:C	W84R	1.000
6:63579001:C:A	A101D	1.000
6:63579004:T:A	V102D	1.000
6:63579009:T:A	C104S	1.000
6:63579009:T:C	C104R	1.000
6:63579010:G:A	C104Y	1.000
6:63579010:G:C	C104S	1.000
6:63579010:G:T	C104F	1.000

dbSNP variants (sampled 300 via entrez): RS1000023914 (6:63523524 T>C), RS1000100161 (6:63532841 A>C), RS1000130102 (6:63557357 G>A), RS1000154491 (6:63582637 G>A), RS1000156309 (6:63538641 A>G), RS1000185087 (6:63582266 A>G), RS1000319228 (6:63544142 T>C), RS1000348042 (6:63527140 A>C,G), RS1000361398 (6:63564035 G>A), RS1000413636 (6:63573983 A>G), RS1000482691 (6:63557639 G>T), RS1000535513 (6:63546910 G>T), RS1000637044 (6:63516630 T>G), RS1000660389 (6:63582401 ATAAAT>A), RS1000770147 (6:63540479 G>A)

Disease associations

OMIM: gene MIM:601585 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004946_57	Schizophrenia	3.000000e-08
GCST90014325_1	Asthma	6.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075169 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 27,049 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL55	PENTAMIDINE	4	27,049

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

6 potent at pChembl≥5 of 15 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	IC50	50	nM	CHEMBL4445621
6.89	IC50	130	nM	CHEMBL3393171
6.77	IC50	170	nM	CHEMBL3393171
6.76	IC50	173	nM	CHEMBL3393171
6.52	IC50	300	nM	PENTAMIDINE
6.17	IC50	676	nM	CHEMBL1088572

PubChem BioAssay actives

6 with measured affinity, of 47 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
7-imino-2-phenylthieno[3,2-c]pyridine-4,6-dione	1634317: Inhibition of PTP4A1 (unknown origin) expressed in Escherichia coli assessed as reduction in hydrolysis using DIFMUP as substrate incubated for 30 mins in presence of DTT by Fluorescence based method	ic50	0.0500	uM
7-amino-2-phenyl-5H-thieno[3,2-c]pyridin-4-one	1759058: Inhibition of full-length human brain His6-tagged PRL-1 expressed in Escherichia coli using TAMRA-Thr-Ala-Asp-Ile-Tyr(PO3H2)-Glu-NH2 peptide as substrate by IMAP-FP assay	ic50	0.1300	uM
Pentamidine	1634308: Inhibition of PTP4A1 (unknown origin)	ic50	0.3000	uM
sodium [6-(2-fluorophenyl)-5,8-dihydro-[1,3]dioxolo[4,5-g]quinolin-8-yl] hydrogen phosphate	463844: Inhibition of human PTP4A1 by enzyme assay	ic50	0.6760	uM

CTD chemical–gene interactions

76 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, increases expression, affects cotreatment, decreases expression	5
Cisplatin	affects cotreatment, decreases expression	3
Dexamethasone	decreases reaction, increases expression, decreases expression, affects cotreatment	3
Estradiol	decreases reaction, increases expression, increases reaction, affects expression	3
bisphenol A	affects expression, affects cotreatment, decreases expression	2
Arsenic	affects methylation, decreases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Valproic Acid	affects expression, increases methylation	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	increases expression	1
deoxynivalenol	increases expression	1
lead acetate	affects cotreatment, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
chromous chloride	affects cotreatment, decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
chromic oxide	affects cotreatment, decreases expression	1
ochratoxin A	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
triacsin C	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentabromodiphenyl ether	increases expression	1
candoxin	decreases expression	1
torcetrapib	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1113383	Binding	Inhibition of human PTP4A1 at 10 uM by enzyme assay	Synthesis and preclinical evaluations of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one monosodium phosphate (CHM-1-P-Na) as a potent antitumor agent. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.